There are some migration scripts you will need to run in order to upgrade your existing databases from 4.x, mainly the system databases in 'mysql' to add support for a few more permission types. These are installed as part of the port.

You will need to import timezone information.

You may also need to set the default charset on your existing databases and rebuild indexes to fix possible collation issues (I don't recall if this is still needed, and in fact I don't think it is strictly needed unless you intend to use any charset but the default).

There may well be other things I have not mentioned, but I think most of the issues in upgrading are more than adequately covered in the mysql documentation, upgrade and release notes.